Abstract The number of people with Down syndrome (DS) living the U.S. has grown from ~50,000 to ~250,700 over the past 70 yrs. Nearly all individuals with DS display pathology associated with Alzheimer's disease (AD) beginning as early as age 30. Previous research in typically developed adults suggests that increased moderate-to-vigorous physical activity (MVPA) may improve cognitive function and protect against age-related structural and functional changes in the brain; however, the potential impact of increased MVPA on the development of AD in adults with DS has not been evaluated. Despite the potential positive impact of MVPA on cognition and AD risk, participation in MVPA among young adults with DS is low. The limited research evaluating strategies for increasing MVPA in adults with DS and has been unsuccessful in increasing short- term (? 12 wks.) or long-term MVPA (12 mo.). Results from our preliminary investigation (12 wks.) which remotely delivers real-time MVPA, led by a trained health coach, to groups of adults with DS in their homes (n=27), via video conferencing on a tablet computer demonstrated high attendance, increased MVPA during group sessions, and improvements in cognitive function. However, the sustainability, impact on total daily MVPA, optimal session frequency, and potential impacts on cognitive function and brain health of remotely delivered group MVPA sessions in adults with DS are unknown. Therefore, we propose a 12 mo. early stage clinical trial in 80 non-demented adults with DS to determine the feasibility and potential efficacy of remotely delivered group MVPA sessions to increase daily MVPA, relative to a usual care control. Participants will be randomized to attend 40 min remotely delivered group MVPA sessions at a low frequency (1 session/wk.,RL), high frequency (3 sessions/wk., RH), or usual care control. Content for both the RL and RH arms will be identical with the exception of group session frequency (1 vs. 3/wk.). Consistent with the funding announcement PAR-18-877 this trial will assess the feasibility and potential effectiveness of the RL, RH, and UC interventions on MVPA, and gather initial estimates of the impact of MVPA on cognition and measure of brain health related to AD in adults with DS. This information is required to inform the development of adequately powered, late stage confirmatory trials to evaluate the role of increased MVPA to prevent or delay AD in adults with DS. Our primary aim will assess daily MVPA (min) in the RL, RH, and UC arms at baseline, 3, 6, 9, and 12 mos., and obtain effect sizes for change in MVPA over 12-mos. Secondary aim 1 will assess the impact of MVPA across the RL, RH, and UC arms on cardiovascular fitness, quality of life, cognitive function and brain parameters related to AD (whole and regional brain volume, functional connectivity, resting state MRI, cerebral blood flow) at baseline, 6, and 12 mos. Secondary aim 2 will determine the feasibility (retention, session attendance, use of recorded sessions (RH/RL only) and safety) of RL, RH, and UC arms.